Although many approaches have been developed for the quick assessment of SARS-CoV-2 infection, few of them are devoted to the detection of the neutralizing antibody, which is essential for assessing the effectiveness of vaccines. Herein, we developed a tri-mode lateral flow immunoassay (LFIA) platform based on gold–silver alloy hollow nanoshells (Au–Ag HNSs) for the sensitive and accurate quantification of neutralizing antibodies. By tuning the shell-to-core ratio, the surface plasmon resonance (SPR) absorption band of the Au–Ag HNSs is located within the near infrared (NIR) region, endowing them with an excellent photothermal effect under the irradiation of optical maser at 808 nm. Further, the Raman reporter molecule 4-mercaptobenzoic acid (MBA) was immobilized on the gold–silver alloy nanoshell to obtain an enhanced SERS signal. Thus, these Au–Ag HNSs could provide colorimetric, photothermal and SERS signals, with which, tri-mode strips for SARS-CoV-2 neutralizing antibody detection were constructed by competitive immunoassay. Since these three kinds of signals could complement one another, a more accurate detection was achieved. The tri-mode LFIA achieved a quantitative detection with detection limit of 20 ng/mL. Moreover, it also successfully detected the serum samples from 98 vaccinated volunteers with 79 positive results, exhibiting great application value in neutralizing antibody detection.

尽管已经开发了许多方法来快速评估 SARS-CoV-2 感染，但很少有方法专门用于检测中和抗体，而中和抗体对于评估疫苗的有效性至关重要。在此，我们开发了一种基于金银合金空心纳米壳（Au-Ag HNSs）的三模式横向流动免疫测定（LFIA）平台，用于中和抗体的灵敏和准确定量。通过调整壳核比，Au-Ag HNSs 的表面等离子共振 (SPR) 吸收带位于近红外 (NIR) 区域，使其在光脉泽照射下具有优异的光热效应808 纳米。此外，将拉曼报告分子 4-巯基苯甲酸 (MBA) 固定在金银合金纳米壳上以获得增强的 SERS 信号。因此，这些 Au-Ag HNSs 可以提供比色、光热和 SERS 信号，利用这些信号，通过竞争免疫分析构建了用于 SARS-CoV-2 中和抗体检测的三模试纸条。由于这三种信号可以相互补充，从而实现了更准确的检测。三模式 LFIA 实现了定量检测，检测限为 20 ng/mL。此外，还成功检测了98名接种疫苗的志愿者的血清样本，结果为79份阳性，在中和抗体检测方面具有很大的应用价值。实现了更准确的检测。三模式 LFIA 实现了定量检测，检测限为 20 ng/mL。此外，还成功检测了98名接种疫苗的志愿者的血清样本，结果为79份阳性，在中和抗体检测方面具有很大的应用价值。实现了更准确的检测。三模式 LFIA 实现了定量检测，检测限为 20 ng/mL。此外，还成功检测了98名接种疫苗的志愿者的血清样本，结果为79份阳性，在中和抗体检测方面具有很大的应用价值。